Metabolic maturation of the human brain from birth through adolescence: insights from in vivo magnetic resonance spectroscopy

Abstract

Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease.

Keywords: human brain maturation; magnetic resonance spectroscopy; metabolism; myelination.

Figure 1.

(Left) T₂-weighted MRI indicating the parietal WM and parietal/occipital GM ROI. (Right) Representative spectra of parietal WM and parietal/occipital GM in subjects with normal MRI at different stages of brain development.

Figure 2.

Representative spectra of fWM, DGN, and brain stem of the newborn brain and at early adolescence.

Figure 3.

Measured concentrations and fitted curves for NAA, creatine (Cr), total choline (Cho), and mI for the various brain regions studied versus age. A logarithmic scale was used for the time-axis (x-axis) to allow a more detailed inspection of age-dependent changes immediately after birth. PCA = postconceptional age.

Figure 4.

Measured concentrations and time courses for glutamate (Glu) and taurine (Tau) for the various brain regions studied versus age. PCA = postconceptional age.